Dendrimers are macromolecules consisting of monomers which are associated according to a tree-structured process around a multifunctional central core.
Dendrimers, also called “cascade molecules”, are highly branched functional polymers with a defined structure. These macromolecules are actually polymers since they are based on the association of recurrent units. However, dendrimers fundamentally differ from conventional polymers insofar that they have specific properties due to their tree-structured construction. The molecular weight and the shape of the dendrimers may be accurately controlled and the functions are located at the ending of the tree-structures, forming a surface, which makes them easily accessible.
Dendrimers are built step by step, by repeating a sequence of reactions allowing the multiplication of each recurrent unit and of the terminal functions. Each sequence of reactions forms what is called a “new generation”. The tree-structured construction is carried out by repeating a sequence of reactions with which a new generation and an increasing number of identical branches may be obtained at the end of each reaction cycle. After a few generations, the dendrimer assumes a highly branched and multifunctionalized globular shape by the numerous terminal functions present at the periphery.
Such polymers were notably described by Launay et al., Angew. Chem. Int. Ed. Engl., 1994, 33, 15/16, 1590-1592, [1] or further Launay et al., Journal of Organometallic Chemistry, 1997, 529, 51-58. [2]
Hypoxic tumors are clinically very difficult to treat: they are resistant to radiation and chemotherapy treatments and are often accrue treatments [3]
However, hypoxic tumor cells are known to be very aggressive and spread rapidly as metastasis throughout the body.[4]
Because hypoxic tumors respond poorly to conventional treatments (radiation and chemotherapy), other therapeutic options have emerged as hyperbaric oxygen, and sensitiving agents by bioreducing action.[5]
In this example, bioreducing agents like family of nitro-imidazole, are reduced by hypoxic tumor cells by intracellular metabolites leading to form anionic radicals which react intracellularly.
Before this “homeless therapeutic” new methods of intra-arterial administration of cytotoxic agents (radiotherapy=yttrium radiation, chemotherapy=doxorubicin and some chemical congeners) have greatly improved the prognosis. [6]
In situ cancer therapy is the solution of choice in the recurrence and metastasis beyond the systemic therapy and for reasons related to resistance or exceeded the tolerated dose for antimitotic used in previous treatments.
In situ radiotherapy by intra arteriography administration is proposed for the treatment of metastases resistant large in relation to their hypoxic state. But so far, this technique uses a non-diffusible generally formed of adsorbed yttrium-90 microspheres.
In the absence of intratumoral diffusion and non-specificity of the product used, this treatment is based solely on the physical path of ionizing radiation, has a very limited effectiveness in the presence of a large tumor.
Accordingly, there is a great need to develop new compounds useful for treatment of cancer, in particular, compounds that may help improve the prognosis of these patients who are currently considered palliative.